Safety and Efficacy of Fruquintinib Plus Chidamide and Sintilimab in the Third and Later Line Treatment of MSS/pMMR Metastatic Colorectal Cancer

Prior treatment

• Concurrent with any of the following conditions: uncontrolled hypertension, coronary artery disease, arrhythmias, and heart failure;
• Previous treatment with small molecule tyrosine kinase inhibitors for metastatic disease;
• Previous treatment with romidepsin;
• Previous treatment with immune checkpoint inhibitors for metastatic disease;
• Uncontrollable severe concurrent infections;
• Acute myocardial infarction, acute coronary syndrome, or CABG within 3 months before the first treatment;

Other illness

• Subjects allergic to the study medication or any of its excipients;

Lab values

• Known human immunodeficiency virus (HIV) infection. Known clinically significant liver disease history, including viral hepatitis \[known carriers of hepatitis B virus (HBV) must exclude active HBV infection, i.e., HBV DNA positive (\>1×10\^4 copies/mL or \>2000 IU/mL); known hepatitis C virus (HCV) infection and HCV RNA positive (\>1×10\^3 copies/mL)\];
  • 12\. Patients whom the investigator deems inappropriate for inclusion in this study.

Other

• Unable to comply with the study protocol or procedures;
• Pregnant or breastfeeding women;

• Fully understand this study and voluntarily sign the informed consent form;
• Age between 18-75 years inclusive;
• Patients with histologically confirmed unresectable locally advanced, recurrent, or metastatic colorectal adenocarcinoma;
• Failure of standard second-line systemic treatment with measurable lesions;
• Tumor tissue tested for microsatellite stability (MSS) or low microsatellite instability (MSI-L) by PCR, or confirmed pMMR by immunohistochemistry for DNA mismatch repair (MMR) protein (including MLH1, MSH2, MSH6, and PMS2 protein expression);
• ECOG performance status of 0-2, with no deterioration within 7 days;
• BMI≥18;
• Expected survival ≥3 months;
• Major organ functions meet the following requirements (no use of any blood components and growth factors within 14 days before enrollment):
  • Absolute neutrophil count ≥1.5×109/L, white blood cells ≥4.0×109/L;
  • Platelets ≥100×109/L;
  • Hemoglobin ≥90g/L;
  • Total bilirubin TBIL ≤1.5 times ULN;
  • ALT and AST ≤5 times ULN;
  • Urea/BUN and creatinine (Cr) ≤1.5×ULN (and creatinine clearance (CCr) ≥ 50mL/min);
  • Left ventricular ejection fraction (LVEF) ≥50%;
  • Corrected QT interval by Fridericia's formula (QTcF) \<470 milliseconds.
  • INR ≤1.5×ULN, APTT ≤1.5×ULN.
• Women of childbearing age must use effective contraception;
• Good compliance and cooperation with follow-up.